title: PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65.
abstract: Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 (PHF20) maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that PHF20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In PHF20 overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between PHF20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that PHF20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies PHF20 as a novel regulator of NF-κB activation and suggests that elevated expression of PHF20 may drive constitutive NF-κB activation in some cancers.
authors.affiliation: Department of Pharmacology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301 747, South Korea.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Zhang
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Park
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Byun
authors.forename: Juhee
authors.initials: J
authors.lastname: Jeon
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Lee
authors.forename: Jang Hee
authors.initials: JH
authors.lastname: Hong
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Seon-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Hyunju
authors.initials: H
authors.lastname: Ro
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Liu
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
authors.forename: Gang Min
authors.initials: GM
authors.lastname: Hur
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C440091:PHF20 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D054648:Protein Phosphatase 2; D008239:Lysine